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Neurons are the primary cells responsible for information processing in the central nervous system (CNS). However, they are vulnerable to damage and insult in a variety of neurological disorders. As the most abundant glial cells in the brain, astrocytes provide crucial support to neurons and participate in synapse formation, synaptic transmission, neurotransmitter recycling, regulation of metabolic processes, and the maintenance of the blood-brain barrier integrity. Though astrocytes play a significant role in the manifestation of injury and disease, they do not work in isolation. Cellular interactions between astrocytes and neurons are essential for maintaining the homeostasis of the CNS under both physiological and pathological conditions. In this review, we explore the diverse interactions between astrocytes and neurons under physiological conditions, including the exchange of neurotrophic factors, gliotransmitters, and energy substrates, and different CNS diseases such as Alzheimer's disease, Parkinson's disease, stroke, traumatic brain injury, and multiple sclerosis. This review sheds light on the contribution of astrocyte-neuron crosstalk to the progression of neurological diseases to provide potential therapeutic targets for the treatment of neurological diseases.
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http://dx.doi.org/10.1007/s11064-024-04241-6 | DOI Listing |
Cell Commun Signal
July 2025
Departament de Biomedicina, Facultat de Medicina i Ciències de la Salut, Institut de Neurociències, Universitat de Barcelona, Barcelona, 08036, Spain.
Background: Deficits in mitochondrial bioenergetics and dynamics are strongly implicated in the selective vulnerability of striatal neurons in Huntington´s disease. Beyond these neuron-intrinsic factor, increasing evidence suggest that non-neuronal mechanisms, particularly astrocytic dysfunction involving disrupted homeostasis and metabolic support also contribute to disease progression. These findings underscore the critical role of metabolic crosstalk between neurons and astrocytes in maintaining striatal integrity.
View Article and Find Full Text PDFMov Disord
July 2025
Qingdao Hospital (Qingdao Municipal Hospital), Qingdao Key Laboratory of Neurorehabilitation, University of Health and Rehabilitation Sciences, Qingdao, Shandong, China.
Astrocytes communicate bidirectionally with neurons. The concerted activity of the neuron-astrocyte system is responsible for the progressive destruction of dopaminergic neurons in Parkinson's disease (PD). There is an urgent need to explore new prevention and treatment strategies for PD because of the lack of effective pharmaceutical therapies.
View Article and Find Full Text PDFAdv Sci (Weinh)
June 2025
Department of Orthopedic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, 150000, P. R. China.
Spinal cord injury (SCI) presents formidable therapeutic challenges due to its multifaceted pathological complexity. Here, this work reports engineered macrophage-derived exosomes overexpressing GNA12 and GNA13 (G12G13MExos) that reprogram macrophages toward the M2c anti-inflammatory phenotype and astrocytes into a neuroprotective phenotype. G12G13MExos enhance astrocyte-mediated clearance of myelin debris, glutamate homeostasis, and synapse formation while fostering astrocyte-neuron crosstalk.
View Article and Find Full Text PDFFront Biosci (Landmark Ed)
May 2025
Neurology Department, The Second Hospital of Hebei Medical University, 050000 Shijiazhuang, Hebei, China.
Background: Multiple sclerosis (MS) is characterized as a chronic inflammatory autoimmune disorder affecting the central nervous system (CNS). Prior research has explored the involvement of pyroptosis and high mobility group box 1 (HMGB1) in the pathophysiology of MS. Nevertheless, the underlying pathogenic mechanisms and their interactions have yet to be fully elucidated.
View Article and Find Full Text PDFJ Huntingtons Dis
August 2025
Department of Biosciences, University of Milan, Milan, Italy.
Astrocytes are key elements for synapse development and function. Several astrocytic dysfunctions contribute to the pathophysiology of various neurodegenerative disorders, including Huntington's disease (HD), an autosomal-dominant neurodegenerative disorder that is characterized by motor and cognitive defects with behavioral/psychiatric disturbances. One dysfunction in HD related to astrocytes is reduced cholesterol synthesis, leading to a decreased availability of local cholesterol for synaptic activity.
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